A new UCL-led study funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF) found that people who injected exenatide once a week for about a year performed better in movement (motor) tests than those who injected a placebo.
‘Activating GLP-1 receptors in the brain by the action of the drug exenatide can boost the function of dopamine connections and improve motor performance in Parkinsonís patients.’
"This is a very promising finding, as the drug holds potential to affect the course of the disease itself, and not merely the symptoms," said the study's senior author, Professor Tom Foltynie (UCL Institute of Neurology). "With existing treatments, we can relieve most of the symptoms for some years, but the disease continues to worsen."
One in 500 people are affected with Parkinson's disease and is the second most common neurodegenerative disease worldwide. The symptoms may not be typically apparent until over 70% of the brain's dopamine-producing cells have been affected.
The effects of Parkinson's disease
Exenatide For Diabetics
- Muscle stiffness
- Slowness of movement
- Sleep disturbance
- Chronic fatigue
- Impaired quality of life
Exenatide has been used since 2005 to treat Type 2 diabetes. The drug activates receptors for the GLP-1 hormone in the pancreas to stimulate insulin release. Activating GLP-1 receptors can boost the function of dopamine connections as they are also found in the brain. It also acts as an anti-inflammatory agent, improves energy production, and switches on cell survival signals.
Exenatide Tested For Parkinson's
A team led by Professor Foltynie seek to clarify how exenatide works for people with Parkinson's disease.
Prior evidence in animal models demonstrated that exenatide improved motor performance. Another study also found early evidence that it could be a disease-modifying agent for Parkinson's, but it was an open-label trial, so this latest study strengthens the existing evidence as the first randomised, placebo-controlled trial of the drug for Parkinson's patients.
"This is the strongest evidence we have so far that a drug could do more than provide symptom relief for Parkinson's disease," said Professor Foltynie.
For the study, the research team followed 60 people with Parkinson's disease at the National Hospital for Neurology and Neurosurgery (NHNN). The patients were given either a once-weekly injection of exenatide for 48 weeks, or a placebo, in addition to their regular medications.
At 48 weeks people who used exenatide had better motor function and the effect persisted after the 12-week follow-up. But those who had injected the placebo showed a decline in their motor scores at both the 48- and 60-week tests. The advantage of 4 points, on a 132-point scale of measures such as tremors, agility and speech, was statistically significant.
"Using approved therapies for one condition to treat another, or drug repurposing, offers new avenues to speed Parkinson's therapeutic development," said Dr Brian Fiske, senior vice president of research programs at MJFF.
"The results from the exenatide studies justify continued testing, but clinicians and patients are urged not to add exenatide to their regimens until more is known about their safety and impact on Parkinson's."
"While we are optimistic about the results of our trial, there is more investigation to be done, and it will be a number of years before a new treatment could be approved and ready for use. We also hope to learn why exenatide appears to work better for some patients than for others," said the study's first author, Dr Dilan Athauda (UCL Institute of Neurology).
The researchers say the next step will be a longer-term study with more participants, which will investigate whether there are marked improvements in quality of life.
- Dilan Athauda et al., Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial, The Lancet (2017)